Review of 3rd Annual Translational Microbiome Conference

James Vitale

Friday, April 28, 2017

This year was the 3rd year of the Translational Microbiome Conference held in Boston, Massachusetts. Boston is a major hub of microbiome research in academia, biotech, and pharma industries. This conference draws attendees from around the world who all want to better understand how the microbiome can be harnessed to improve human health.

New this year were workshops held the day before the general sessions began. One workshop titled Navigating the Challenges of Studying the Microbiome in Mouse Models: Design, Execution and Utility led by Alexander Maue, PhD, director of microbiome products and services at Taconic Biosciences and R. William DePaolo, PhD, associate professor of medicine at the University of Washington and Director, Center for Microbiome Sciences & Therapeutics (CMiST). In this workshop, participants discussed best practices for performing in vivo microbiome studies in mice in breakout groups led by Beth McCormick, PhD, executive director at the University of Massachusetts Center for Microbiome. Further discussions included whether germ-free mice that have had their gut flora depleted with antibiotics are the best in vivo model for studying the microbiome and how to collect, store, and administer samples when performing a fecal microbiota transfer. James Matumba, PhD, co-founder of CommenSe and senior associate at PureTech provided key insights on moving from research results to the clinic.

The general session kicked off with a keynote address from Jack Gilbert, PhD, faculty director of the Microbiome Center at the University of Chicago. Dr. Gilbert has published extensively in the emerging microbiome field. His address focused on "applying new strategies to identify how the microbial ecosystem correlates with disease states and treatment efficacy through Microbiome-Wide Association Studies (MWAS). MWAS is altering the trajectory of precision medicine, and providing a new framework for facilitating patient care." Dr. Gilbert noted that we are "microbially unique" leading to the need for precision medicine and even probiotics. He also noted there are 399 clinical microbiome trials ongoing. Dr. Gilbert's keynote address set the tone in reminding the audience how they can positively affect precision medicine.

Henry Haiser, PhD, an investigator from Novartis Institutes for BioMedical Research (NIBR) spoke on how NIBR is leveraging the knowledge emerging from microbiome research. Within the Chemical Biology & Therapeutics Department at NIBR, they are "focusing on uncovering small molecule mediators of disease-relevant microbes/host interactions and identifying new pharmacological targets that assimilate microbiome-derived signals." In other words, NIBR is using the microbiome as a source of new small molecule targets. They apply their extensive background in small molecule discovery to their microbiome research.

Arpita Maiti, head of external R&D at Pfizer spoke to the central challenges on the path to approved microbiome therapeutics. Microbiome manufacturing requires a different approach to fabricate consistent product and cross fertilization from other sectors may be necessary. Anaerobic scale-up can be a challenge and may be more complicated than producing large molecules (i.e. monoclonal antibodies). Ms. Maiti noted that in clinical development, much thought will be required to understand how trials should be designed with new modalities and what will be required to demonstrate efficacy. It is unclear how regulatory agencies such as the FDA and EMA will assess new products and modalities as chronic therapies. Some considerations will be pricing versus standard of care which will include biologics and biosimilars.

A presentation by Randi Lundberg, DVM, application scientist at Taconic Biosciences entitled Mice as Translational Models: Planning a Fecal Microbiota Transplantation Study, covered practical considerations and pitfalls when planning experiments using gnotobiotic mice generated by fecal microbiota transplantation. She spoke about recipients such as germ-free mice and antibiotic depleted mice and how these two different starting points can affect FMT studies. Dr. Lundberg also focused on how housing modalities, such as isolator or individually ventilated cage housing can affect study outcomes.

Also important to translation of research studies to the clinic is how data is analyzed and results interpreted. In her presentation, Tools to Improve the Reproducibility of Microbiome Sequencing, Cheryl-Emiliane Chow, PhD, bioinformatics scientist at Second Genome Solutions, explained how "microbiome profiling, the characterization of the identity, and function of all microbes within a given environment, is a growing and emerging dimension of human health research." Dr. Chow highlighted one of the proprietary tools they use, Phylochip™. Phylochip™ provides comprehensive coverage of the entire 16S rRNA gene. This enables high resolution classification using 1 million probes representing all annotated bacteria/archea genes. There are multiple probes for every known category of bacteria, giving the ability to measure ~60,000 bacterial operational taxonomic units at once. Dr. Chow noted to have actionable insights, you need to have confidence in the data. Low abundance taxa can have high impact. Confidence in detection of shifts is therefore key.

In the second Keynote Address, Metagenomics in Understanding Human Biology, Disease and the Environment, Rita Colwell, PhD, distinguished professor at the University of Maryland at College Park and president at CosmosID, Inc., explained how high-throughput sequencing, combined with high-resolution bioinformatics provides a powerful tool for microbiome studies as well as clinical management of infectious diseases. The microbiome is complex, but we need to be succinct and concise in communication of results.

Also new this year was a Consumer Health Track with talks focused on the role of the microbiome in consumer health. These presentations ranged from women's health, to immunomodulation, and a panel discussion with the intriguing title of, Time to Put the Hygiene Hypothesis to Rest?. Discussion centered on how to instruct the public on what organisms are commensal and which are pathogenic. Another topic of conversation, focused on how can hygiene be imparted in a way that protects the "good" microbes while removing or killing pathogenic organisms.

Rounding out this track was a talk from Lihi Segal, co-founder and CEO of Day Two. In her presentation, Personalized Nutrition Using Gut Microbiome and Clinical Data, Ms. Segal discussed how certain eating behaviors can result in major risk factors for life threatening diseases. She notes "research from the Weizmann Institute in Israel found high variability in individual response to identical meals, with the gut microbiome being a major driver of interpersonal variability." Her company, Day Two, uses an algorithm to provide personalized nutrition and actionable insight that allows people to maintain normal blood sugar levels. Is there a best diet for humans? This could be the wrong question. One must consider nutrition, genetics, microbes, and how lifestyle affects health leading to personalized nutrition. Instead Segal suggests we should ask, "What's the best diet for me?".

This summary highlights only a small portion of the presentations and discussions from this year's Translational Microbiome Conference. The output of this meeting demonstrates how much focus there is on translational microbiome research, but particularly how we are moving towards treatments for people who are suffering from diseases associated with alterations in their microbiome. If you missed this year's Translational Microbiome Conference, plans are already underway for next year's conference.